Enzyme neuron-specific enolase

The immunohistochemical demonstration of the specific endocrine cell peptides allows the classification of the pancreatic endocrine neoplasms (PENs). However, it is not always possible to demonstrate these in PENs. Therefore it is of diagnostic importance to use broad-spectrum endocrine cell markers for the general identification of the endocrine nature of islet cells and PENs. These protein markers, localized in the secretory granules in the cytosol or in the cellular membrane, are present in most (rarely in all) normal and neoplastic endocrine cells. The markers most commonly used in routine histopathology have been the secretory granule proteins chromogranin and synaptophysin and the cytosolic enzyme neuron-specific enolase (NSE). Of these, chromogranin is the most specific but its sensitivity is about 80% to 90% (Fig. 15.2). 

Enolase is a glycolytic enzyme also known as phosphopyru-vate hydratase. Neuron-specific enolase (NSE) is the form of enolase found in neuronal tissue and in the cells of the diffuse neuroendocrine system and the amine precursor uptake, and decarboxylation (APUD) tissue. NSE is found in tumors associated with the neuroendocrine origin, including small cell lung cancer (SCLC), neuroblastoma, pheochromocytoma, carcinoid, medullary carcinoma of the thyroid, melanoma, and pancreatic endocrine tumors. 

The enolase enzymes comprise five different forms, each of which is composed of three homodimers and two hybrids. Neuron-specific enolase (NSE) is found in a variety of normal and neoplastic neuroendocrine cells and predominates in the brain. Originally believed to be a specific marker for neuroendocrine differentiation, it has subsequently been observed that NSE can be found in virtually any type of neoplasm. Because of this, it is a poor antibody to use to screen for neuroendocrine differentiation. Overall a poor marker for detection of neuroendocrine differentiation because of its lack of specificity, NSE may be useful in combination with other more specific antibodies such as chromogranin and synaptophysin for the appropriate neuroendocrine morphologic identification and documentation of immunostaining. 

FIGURE 10.38 Distribution of markers in pancreatic endocrine tumors. SYN, synaptophysin NSE, neuron-specific enolase LMWCK, low-molecular-weight cytokeratin CgA, chromogranin A PC2, pro-convertase 2 PCM, peptidylglycine alpha-amidating enzyme PC3, proconvertase 3 NFP, neurofilament protein HCC(a), human chorionic gonadotropin alpha VIM, vimentin. 

Neuron-specific enolase neuron-specific enolase (NSE) is a glycolytic enzyme catalyzing the reaction pathway between 2-phospho-glycerate and phosphophenol pyruvate. Enolases are homo or heterodimers composed of the three subunits 46-kDa alpha (a)-subunit, 44-kDa beta (P)-subunit and 46-kDa gamma (Y)-subunit. The a-subunit is expressed in most tissue types while the expression of the P-subunit is restricted mainly to the striated muscle including skeletal muscle and myocardium. The y-subunit is expressed primarily in neurons, in normal and in neoplastic neuroendocrine cells, but it can be also expressed in megakaryocytes, T-lymphocytes in addition to striated and smooth muscle cells. The y-dimeric (y-y)... 

Schmechel DE. Gamma subunit of the glycolytic enzyme enolase Nonspecific or neuron specific Lab Invest. 1985 52 239-242. 

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